Early life, adiposity rebound, and puberty represent critical growth periods when food choices co... more Early life, adiposity rebound, and puberty represent critical growth periods when food choices could have long-term relevance for cancer risk. We aimed to relate dietary patterns during these periods to the growth hormone-insulin-like-growth-factor (GH-IGF) axis, insulin resistance, and body fatness in adulthood. Data from the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study participants with outcome data at 18-37 years, and ≥2 dietary records during early life (1-2 yr; n = 128), adiposity rebound (4-6 years, n = 179), or puberty (girls 9-14, boys 10-15 yr; n = 213) were used. Dietary patterns at these ages were derived by 1) reduced rank regression (RRR) to explain variation in adult IGF-I, IGF-binding protein-3 (IGFBP-3), homoeostasis model assessment for insulin resistance (HOMA-IR) and fat-mass index; 2) principal component analysis (PCA). Regarding RRR, the patterns "cake/canned fruit/cheese & eggs" (early life), "sweets & dairy" (adiposity rebound) and "high-fat foods" (pubertal boys) were independently associated with higher adult HOMA-IR. Furthermore, the patterns "favorable carbohydrate sources" (early life), "snack & convenience foods" (adiposity rebound), and "traditional & convenience carbohydrates" (pubertal boys) were related to adult IGFBP-3 (P trend < 0.01). PCA identified "healthy" patterns for all periods, but none was associated with the outcomes (P trend > 0.1). In conclusion, dietary patterns during sensitive growth periods may be of long-term relevance for adult insulin resistance and IGFBP-3.
Steroids are primarily present in human fluids in their sulfated forms. Profiling of these compou... more Steroids are primarily present in human fluids in their sulfated forms. Profiling of these compounds is important from both diagnosis and physiological points of view. Here, we present a novel method for the quantification of 11 intact steroid sulfates in human serum by liquid chromatography-tandem mass spectrometry. The compounds analyzed in our method, some of which are quantified for the first time in blood, include cholesterol sulfate, pregnenolone sulfate, 17-hydroxy-pregnenolone sulfate, 16-alpha-hydroxy-dehydroepiandrosterone sulfate, dehydroepiandrosterone sulfate, androstenediol sulfate, androsterone sulfate, epiandrosterone sulfate, testosterone sulfate, epitestosterone sulfate and dihydrotestosterone sulfate. The assay was conceived to quantify sulfated steroids in a broad range of concentrations, requiring only 300 microliters of serum. The method has been validated and its performance was studied at three quality controls, selected for each compound according to its physiological concentration. The assay showed good linearity (R2>0.99) and recovery for all the compounds, with limits of quantification ranging between 1 ng/ml and 80 ng/ml. Averaged intra-day and between-day precisions (CV) and accuracies (relative errors) were below 10%. The method has been successfully applied to study the sulfated steroidome in diseases such as steroid sulfatase deficiency, proving its diagnostic value. This is, to our best knowledge, the most comprehensive method available for the quantification of sulfated steroids in human blood.
Steroid sulfatase (STS) deficiency is the underlying cause of the skin condition known as recessi... more Steroid sulfatase (STS) deficiency is the underlying cause of the skin condition known as recessive X-linked ichthyosis (RXLI). RXLI patients show scales on their skin caused by high concentrations of cholesterol sulfate (CS), as they are not capable of releasing the sulfate group from its structure to obtain free cholesterol. CS has been reported, so far, as the sole sulfated steroid with increased concentrations in the blood of RXLI patients. A non-targeted LC-MS approach in negative mode detection (LC-MS precursor ion scan mode) was applied to serum samples of 12 RXLI patients and 19 healthy males. We found that CS was not the only sulfated compound consistently elevated in RXLI patients, because a group of compounds with a m/z of 481 was found in high concentrations too. Further LC-MS/MS demonstrated that the main contributor to the m/z 481 signal in RXLI serum is 27-hydroxycholesterol-3-sulfate (27OHC3S). Accordingly, a new method for 27OHC3S quantification in the context of RX...
Traditional interpretation of GC-MS output involved the semi-quantitative estimation of outstandi... more Traditional interpretation of GC-MS output involved the semi-quantitative estimation of outstanding low or high specific metabolites and the ratio between metabolites. Here, we utilize a systems biology approach to steroid metabolomics of a complex steroid-related disorder, using an all-inclusive analysis of the steroidal pathway in the form of a subject steroidal fingerprint and disease signature, providing novel methods of normalization and visualization. The study compares 324 normal children to pure enzymatic deficiency in 27 untreated 21-hydroxylase CAH patients and to complex disease in 70 children with obesity. Steroid profiles were created by quantitative data generated by GC-MS analyses. A novel peer-group normalization method defined each individual subject's control group in a multi-dimensional space of metadata parameters. Classical steroid pathway visualization was enhanced by adding urinary end-product sub-nodes and by color coding of semi-quantitative metabolic co...
The Journal of steroid biochemistry and molecular biology, 2012
Aldosterone, the most important human mineralocorticoid, is involved in the regulation of the blo... more Aldosterone, the most important human mineralocorticoid, is involved in the regulation of the blood pressure and has been reported to play a key role in the formation of arterial hypertension, heart failure and myocardial fibrosis. Aldosterone synthase (CYP11B2) catalyzes the biosynthesis of aldosterone by successive 11β- and 18-hydroxylation followed by an 18-oxidation of 11-deoxycorticosterone and thus comprises an important drug target. For more than 20 years, all attempts to purify recombinant human CYP11B2 in significant amounts for detailed analysis failed due to its hydrophobic nature as a membrane protein. Here, we present the successful expression of the protein in E. coli yielding approx. 90 nmol/l culture, its purification and detailed enzymatic characterization. Biochemical analyses have been performed using in vitro conversion assays which revelead a V(max) of 238±8 nmol products/nmol hCYP11B2/min and a K(m) of 103±8 μM 11-deoxycorticosterone. Furthermore, binding analy...
Anthropometric measurements are widely used to determine body composition, especially in children... more Anthropometric measurements are widely used to determine body composition, especially in children. Our aim was to compare 2 of the simplest anthropometry-based equations available for determining nutritional status and muscularity in children and adolescents, examined in relation to other methodologically independent muscle variables. Midupper arm muscle area (UAMA) and fat-free mass (FFM) according to the equations of Slaughter et al (Hum Biol 1988;60:709-23), as well as separate biochemical, physical, and radiologic muscle variables, were determined cross-sectionally in 91 males and 91 females aged 6-18 y. The ability of UAMA and FFM to estimate muscularity, as measured by 24-h creatinine excretion, grip force, and peripheral quantitative computer tomography analysis of forearm muscle, was compared after dividing the study population into prepubertal and pubertal groups. Before puberty, correlations of all 3 muscularity variables were higher with FFM than with UAMA in both males a...
Hypercortisolemia in depressed patients is known to be related to changes in body composition, es... more Hypercortisolemia in depressed patients is known to be related to changes in body composition, especially increased ectopic fat and lowered bone mineral density. Both hypercortisolemia in patients with Cushing's disease and depression in patients undergoing treatment with hemodialysis have been shown to be associated with increased left ventricular mass. Increased activity of the hypothalamus-pituitary-adrenal (HPA) system in depressed patients is related to high left ventricular mass. To corroborate our hypothesis, we measured left ventricular mass in 5 depressed patients with clear evidence for HPA system activation (nonsuppression in dexamethasone suppression test [DST]; increased 24 h cortisol excretion) and 27 healthy controls. We found increased left ventricular mass in hypercortisolemic depressed patients compared to healthy controls (343±97 vs. 176±57 gr; p=0.007). Depression is known to be related to an increased risk of cardial morbidity and mortality, although the ris...
Whether higher production of glucocorticoids (GCs) within the physiological range may already be ... more Whether higher production of glucocorticoids (GCs) within the physiological range may already be affecting bone status in healthy children is unknown. Because dietary protein intake affects both bone and GCs, we examined the association of urinary measures of glucocorticoid status and cortical bone in healthy non-obese children, after particularly controlling for protein intake. Proximal forearm bone parameters were measured by peripheral quantitative computed tomography (pQCT). Subjects studied (n = 175, 87 males, aged 6 to 18 years) had two 24-hour urine samples collected: the first sample at 1 year before bone measurement, and the second sample at the time of bone measurement. Major urinary GC metabolites were measured by mass spectrometry and summed to assess daily adrenal GC secretion (∑C21). Urinary free cortisol (UFF) and cortisone (UFE) were summed to assess potentially bioactive free GCs (UFF + UFE). After controlling for several covariates and especially urinary nitrogen (the biomarker of protein intake) cortisol secretion ∑C21 was inversely associated with all analyzed pQCT measures of bone quality. ∑C21 also predicted a higher endosteal and lower periosteal circumference, explaining both a smaller cortical area and (together with lower BMD) a lower strength-strain-index (SSI). UFF + UFE, UFE itself, and a urinary metabolite-estimate of 11beta-hydroxysteroid dehydrogenase type1 (11beta-HSD1) activity showed corresponding reciprocal associations (p < 0.05) with BMD and bone mineral content, but not with SSI and bone geometry variables. In conclusion, higher GC levels, even within the physiological range, appear to exert negative influences on bone modeling and remodeling already during growth. Our physiological data also suggest a relevant role of cortisone as the direct source for intracrine-generated cortisol by bone cell 11beta-HSD1.
The Journal of Steroid Biochemistry and Molecular Biology, 2014
Patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) have an imp... more Patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) have an impaired cortisol synthesis, but it is unknown whether the metabolism of glucocorticoids differs between neonates and infants with and without 21OHD. The objective of this study was to compare the glucocorticoid metabolism between neonates and infants with and without 21OHD. We analyzed 14 urinary glucocorticoid metabolites, 7 metabolites each of cortisol and cortisone, by gas chromatography-mass spectrometry of 89 untreated 21OHD neonates and infants and 161 neonates and infants without 21OHD. Neonates with 21OHD exhibit elevated relative amounts of cortisol metabolites in total glucocorticoid metabolism and an increased ratio of cortisol to cortisone metabolites (p<0.0001). This reflects a shift toward cortisol in the relative balance of the interconversion between cortisol and cortisone. The ratio of cortisol to cortisone metabolites correlated significantly with low urinary glucocorticoid concentrations (p<0.03), with low 21-hydroxylase activity (p<0.001) and high urinary sodium and chloride concentrations (p<0.05) in neonates with 21OHD. Our results demonstrate substantial changes in the relative cortisone to cortisol interconversion in neonates with 21OHD. The shift of glucocorticoid metabolism toward active cortisol in neonates with 21OHD seems to be related to the severity of 21OHD and adrenal dysfunction. Our data provide new insights into the regulation of glucocorticoid homeostasis in 21OHD.
To characterize the urinary steroid metabolome of neonates and infants born either at term or pre... more To characterize the urinary steroid metabolome of neonates and infants born either at term or preterm. We retrospectively analyzed urinary steroid hormone metabolites determined by gas chromatography-mass spectrometry of 78 neonates and infants born at term and 83 neonates and infants born preterm (median 34 weeks of gestational age). The subjects' 11β-hydroxylase and 21-hydroxylase activities were assessed on the basis of urinary metabolite substrate-to-product ratios. Preterm neonates and infants had elevated urinary concentrations of 17α-hydroxyprogesterone (17OHP) metabolites (P<.001) but lower urinary concentrations of the 21-deoxycortisol metabolite pregnanetriolone (PTO) (P<.01). One reason was lower 11β-hydroxylase activity in preterms. We could demonstrate a correlation between low 11β-hydroxylase activity and high urinary concentrations of 17OHP metabolites (r=0.51, P<.001) but low urinary concentrations of the 21-deoxycortisol metabolite PTO (r=-0.24, P=.03) in preterms. Low 11β-hydroxylase activity may explain increased 17OHP but decreased 21-deoxycortisol metabolite excretion in preterms. Our analysis clarifies, first, why preterms have higher 17OHP levels and thus higher rates of false-positive screening results for congenital adrenal hyperplasia than do term infants, and, second, why 21-deoxycortisol or its urinary metabolite PTO is more specific than 17OHP for the diagnosis of 21-hydroxylase deficiency.
Fruit and vegetable (FV) consumption and salt intake are known dietary influences on blood pressu... more Fruit and vegetable (FV) consumption and salt intake are known dietary influences on blood pressure (BP) in adults, but data on their long-term relevance during growth for later BP are rare. We aimed to examine the independent and concomitant influences of adolescent FV and salt intakes on BP in young adulthood. In total, 206 participants (108 males) provided a plausible BP measurement in young adulthood (18-25 years) as well as three repeated 3-day weighed dietary records, 24-h urine samples and BP measurements during adolescence (11-16 years). FV intake was assessed based on dietary records and its urinary biomarkers such as potassium, oxalate and hippuric acid. Urinary sodium chloride (NaCl) was used to estimate salt intake. Prospective associations of adolescent FV and salt intake with adult BP were examined in sex-stratified linear regression models. In multivariable models, a 100 g higher FV intake during adolescence was prospectively related to 0.9 mmHg lower systolic BP in young adult females (P = 0.02), but not in males (P = 0.8). Biomarkers supported the findings for FV regarding systolic BP. Concurrently, a 1 g higher salt intake was related to 1.7 mmHg higher systolic BP in young men only (P = 0.01). For diastolic BP, results were inconsistent. Our findings suggest that in adolescent healthy girls, a higher FV intake may be more relevant for BP than a reduced salt intake and the opposite appears to apply for boys. The physiological implications of the observed sex-specific diet-BP relationships need deeper examination.
Early life, adiposity rebound, and puberty represent critical growth periods when food choices co... more Early life, adiposity rebound, and puberty represent critical growth periods when food choices could have long-term relevance for cancer risk. We aimed to relate dietary patterns during these periods to the growth hormone-insulin-like-growth-factor (GH-IGF) axis, insulin resistance, and body fatness in adulthood. Data from the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study participants with outcome data at 18-37 years, and ≥2 dietary records during early life (1-2 yr; n = 128), adiposity rebound (4-6 years, n = 179), or puberty (girls 9-14, boys 10-15 yr; n = 213) were used. Dietary patterns at these ages were derived by 1) reduced rank regression (RRR) to explain variation in adult IGF-I, IGF-binding protein-3 (IGFBP-3), homoeostasis model assessment for insulin resistance (HOMA-IR) and fat-mass index; 2) principal component analysis (PCA). Regarding RRR, the patterns "cake/canned fruit/cheese & eggs" (early life), "sweets & dairy" (adiposity rebound) and "high-fat foods" (pubertal boys) were independently associated with higher adult HOMA-IR. Furthermore, the patterns "favorable carbohydrate sources" (early life), "snack & convenience foods" (adiposity rebound), and "traditional & convenience carbohydrates" (pubertal boys) were related to adult IGFBP-3 (P trend < 0.01). PCA identified "healthy" patterns for all periods, but none was associated with the outcomes (P trend > 0.1). In conclusion, dietary patterns during sensitive growth periods may be of long-term relevance for adult insulin resistance and IGFBP-3.
Steroids are primarily present in human fluids in their sulfated forms. Profiling of these compou... more Steroids are primarily present in human fluids in their sulfated forms. Profiling of these compounds is important from both diagnosis and physiological points of view. Here, we present a novel method for the quantification of 11 intact steroid sulfates in human serum by liquid chromatography-tandem mass spectrometry. The compounds analyzed in our method, some of which are quantified for the first time in blood, include cholesterol sulfate, pregnenolone sulfate, 17-hydroxy-pregnenolone sulfate, 16-alpha-hydroxy-dehydroepiandrosterone sulfate, dehydroepiandrosterone sulfate, androstenediol sulfate, androsterone sulfate, epiandrosterone sulfate, testosterone sulfate, epitestosterone sulfate and dihydrotestosterone sulfate. The assay was conceived to quantify sulfated steroids in a broad range of concentrations, requiring only 300 microliters of serum. The method has been validated and its performance was studied at three quality controls, selected for each compound according to its physiological concentration. The assay showed good linearity (R2>0.99) and recovery for all the compounds, with limits of quantification ranging between 1 ng/ml and 80 ng/ml. Averaged intra-day and between-day precisions (CV) and accuracies (relative errors) were below 10%. The method has been successfully applied to study the sulfated steroidome in diseases such as steroid sulfatase deficiency, proving its diagnostic value. This is, to our best knowledge, the most comprehensive method available for the quantification of sulfated steroids in human blood.
Steroid sulfatase (STS) deficiency is the underlying cause of the skin condition known as recessi... more Steroid sulfatase (STS) deficiency is the underlying cause of the skin condition known as recessive X-linked ichthyosis (RXLI). RXLI patients show scales on their skin caused by high concentrations of cholesterol sulfate (CS), as they are not capable of releasing the sulfate group from its structure to obtain free cholesterol. CS has been reported, so far, as the sole sulfated steroid with increased concentrations in the blood of RXLI patients. A non-targeted LC-MS approach in negative mode detection (LC-MS precursor ion scan mode) was applied to serum samples of 12 RXLI patients and 19 healthy males. We found that CS was not the only sulfated compound consistently elevated in RXLI patients, because a group of compounds with a m/z of 481 was found in high concentrations too. Further LC-MS/MS demonstrated that the main contributor to the m/z 481 signal in RXLI serum is 27-hydroxycholesterol-3-sulfate (27OHC3S). Accordingly, a new method for 27OHC3S quantification in the context of RX...
Traditional interpretation of GC-MS output involved the semi-quantitative estimation of outstandi... more Traditional interpretation of GC-MS output involved the semi-quantitative estimation of outstanding low or high specific metabolites and the ratio between metabolites. Here, we utilize a systems biology approach to steroid metabolomics of a complex steroid-related disorder, using an all-inclusive analysis of the steroidal pathway in the form of a subject steroidal fingerprint and disease signature, providing novel methods of normalization and visualization. The study compares 324 normal children to pure enzymatic deficiency in 27 untreated 21-hydroxylase CAH patients and to complex disease in 70 children with obesity. Steroid profiles were created by quantitative data generated by GC-MS analyses. A novel peer-group normalization method defined each individual subject's control group in a multi-dimensional space of metadata parameters. Classical steroid pathway visualization was enhanced by adding urinary end-product sub-nodes and by color coding of semi-quantitative metabolic co...
The Journal of steroid biochemistry and molecular biology, 2012
Aldosterone, the most important human mineralocorticoid, is involved in the regulation of the blo... more Aldosterone, the most important human mineralocorticoid, is involved in the regulation of the blood pressure and has been reported to play a key role in the formation of arterial hypertension, heart failure and myocardial fibrosis. Aldosterone synthase (CYP11B2) catalyzes the biosynthesis of aldosterone by successive 11β- and 18-hydroxylation followed by an 18-oxidation of 11-deoxycorticosterone and thus comprises an important drug target. For more than 20 years, all attempts to purify recombinant human CYP11B2 in significant amounts for detailed analysis failed due to its hydrophobic nature as a membrane protein. Here, we present the successful expression of the protein in E. coli yielding approx. 90 nmol/l culture, its purification and detailed enzymatic characterization. Biochemical analyses have been performed using in vitro conversion assays which revelead a V(max) of 238±8 nmol products/nmol hCYP11B2/min and a K(m) of 103±8 μM 11-deoxycorticosterone. Furthermore, binding analy...
Anthropometric measurements are widely used to determine body composition, especially in children... more Anthropometric measurements are widely used to determine body composition, especially in children. Our aim was to compare 2 of the simplest anthropometry-based equations available for determining nutritional status and muscularity in children and adolescents, examined in relation to other methodologically independent muscle variables. Midupper arm muscle area (UAMA) and fat-free mass (FFM) according to the equations of Slaughter et al (Hum Biol 1988;60:709-23), as well as separate biochemical, physical, and radiologic muscle variables, were determined cross-sectionally in 91 males and 91 females aged 6-18 y. The ability of UAMA and FFM to estimate muscularity, as measured by 24-h creatinine excretion, grip force, and peripheral quantitative computer tomography analysis of forearm muscle, was compared after dividing the study population into prepubertal and pubertal groups. Before puberty, correlations of all 3 muscularity variables were higher with FFM than with UAMA in both males a...
Hypercortisolemia in depressed patients is known to be related to changes in body composition, es... more Hypercortisolemia in depressed patients is known to be related to changes in body composition, especially increased ectopic fat and lowered bone mineral density. Both hypercortisolemia in patients with Cushing's disease and depression in patients undergoing treatment with hemodialysis have been shown to be associated with increased left ventricular mass. Increased activity of the hypothalamus-pituitary-adrenal (HPA) system in depressed patients is related to high left ventricular mass. To corroborate our hypothesis, we measured left ventricular mass in 5 depressed patients with clear evidence for HPA system activation (nonsuppression in dexamethasone suppression test [DST]; increased 24 h cortisol excretion) and 27 healthy controls. We found increased left ventricular mass in hypercortisolemic depressed patients compared to healthy controls (343±97 vs. 176±57 gr; p=0.007). Depression is known to be related to an increased risk of cardial morbidity and mortality, although the ris...
Whether higher production of glucocorticoids (GCs) within the physiological range may already be ... more Whether higher production of glucocorticoids (GCs) within the physiological range may already be affecting bone status in healthy children is unknown. Because dietary protein intake affects both bone and GCs, we examined the association of urinary measures of glucocorticoid status and cortical bone in healthy non-obese children, after particularly controlling for protein intake. Proximal forearm bone parameters were measured by peripheral quantitative computed tomography (pQCT). Subjects studied (n = 175, 87 males, aged 6 to 18 years) had two 24-hour urine samples collected: the first sample at 1 year before bone measurement, and the second sample at the time of bone measurement. Major urinary GC metabolites were measured by mass spectrometry and summed to assess daily adrenal GC secretion (∑C21). Urinary free cortisol (UFF) and cortisone (UFE) were summed to assess potentially bioactive free GCs (UFF + UFE). After controlling for several covariates and especially urinary nitrogen (the biomarker of protein intake) cortisol secretion ∑C21 was inversely associated with all analyzed pQCT measures of bone quality. ∑C21 also predicted a higher endosteal and lower periosteal circumference, explaining both a smaller cortical area and (together with lower BMD) a lower strength-strain-index (SSI). UFF + UFE, UFE itself, and a urinary metabolite-estimate of 11beta-hydroxysteroid dehydrogenase type1 (11beta-HSD1) activity showed corresponding reciprocal associations (p < 0.05) with BMD and bone mineral content, but not with SSI and bone geometry variables. In conclusion, higher GC levels, even within the physiological range, appear to exert negative influences on bone modeling and remodeling already during growth. Our physiological data also suggest a relevant role of cortisone as the direct source for intracrine-generated cortisol by bone cell 11beta-HSD1.
The Journal of Steroid Biochemistry and Molecular Biology, 2014
Patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) have an imp... more Patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) have an impaired cortisol synthesis, but it is unknown whether the metabolism of glucocorticoids differs between neonates and infants with and without 21OHD. The objective of this study was to compare the glucocorticoid metabolism between neonates and infants with and without 21OHD. We analyzed 14 urinary glucocorticoid metabolites, 7 metabolites each of cortisol and cortisone, by gas chromatography-mass spectrometry of 89 untreated 21OHD neonates and infants and 161 neonates and infants without 21OHD. Neonates with 21OHD exhibit elevated relative amounts of cortisol metabolites in total glucocorticoid metabolism and an increased ratio of cortisol to cortisone metabolites (p<0.0001). This reflects a shift toward cortisol in the relative balance of the interconversion between cortisol and cortisone. The ratio of cortisol to cortisone metabolites correlated significantly with low urinary glucocorticoid concentrations (p<0.03), with low 21-hydroxylase activity (p<0.001) and high urinary sodium and chloride concentrations (p<0.05) in neonates with 21OHD. Our results demonstrate substantial changes in the relative cortisone to cortisol interconversion in neonates with 21OHD. The shift of glucocorticoid metabolism toward active cortisol in neonates with 21OHD seems to be related to the severity of 21OHD and adrenal dysfunction. Our data provide new insights into the regulation of glucocorticoid homeostasis in 21OHD.
To characterize the urinary steroid metabolome of neonates and infants born either at term or pre... more To characterize the urinary steroid metabolome of neonates and infants born either at term or preterm. We retrospectively analyzed urinary steroid hormone metabolites determined by gas chromatography-mass spectrometry of 78 neonates and infants born at term and 83 neonates and infants born preterm (median 34 weeks of gestational age). The subjects' 11β-hydroxylase and 21-hydroxylase activities were assessed on the basis of urinary metabolite substrate-to-product ratios. Preterm neonates and infants had elevated urinary concentrations of 17α-hydroxyprogesterone (17OHP) metabolites (P<.001) but lower urinary concentrations of the 21-deoxycortisol metabolite pregnanetriolone (PTO) (P<.01). One reason was lower 11β-hydroxylase activity in preterms. We could demonstrate a correlation between low 11β-hydroxylase activity and high urinary concentrations of 17OHP metabolites (r=0.51, P<.001) but low urinary concentrations of the 21-deoxycortisol metabolite PTO (r=-0.24, P=.03) in preterms. Low 11β-hydroxylase activity may explain increased 17OHP but decreased 21-deoxycortisol metabolite excretion in preterms. Our analysis clarifies, first, why preterms have higher 17OHP levels and thus higher rates of false-positive screening results for congenital adrenal hyperplasia than do term infants, and, second, why 21-deoxycortisol or its urinary metabolite PTO is more specific than 17OHP for the diagnosis of 21-hydroxylase deficiency.
Fruit and vegetable (FV) consumption and salt intake are known dietary influences on blood pressu... more Fruit and vegetable (FV) consumption and salt intake are known dietary influences on blood pressure (BP) in adults, but data on their long-term relevance during growth for later BP are rare. We aimed to examine the independent and concomitant influences of adolescent FV and salt intakes on BP in young adulthood. In total, 206 participants (108 males) provided a plausible BP measurement in young adulthood (18-25 years) as well as three repeated 3-day weighed dietary records, 24-h urine samples and BP measurements during adolescence (11-16 years). FV intake was assessed based on dietary records and its urinary biomarkers such as potassium, oxalate and hippuric acid. Urinary sodium chloride (NaCl) was used to estimate salt intake. Prospective associations of adolescent FV and salt intake with adult BP were examined in sex-stratified linear regression models. In multivariable models, a 100 g higher FV intake during adolescence was prospectively related to 0.9 mmHg lower systolic BP in young adult females (P = 0.02), but not in males (P = 0.8). Biomarkers supported the findings for FV regarding systolic BP. Concurrently, a 1 g higher salt intake was related to 1.7 mmHg higher systolic BP in young men only (P = 0.01). For diastolic BP, results were inconsistent. Our findings suggest that in adolescent healthy girls, a higher FV intake may be more relevant for BP than a reduced salt intake and the opposite appears to apply for boys. The physiological implications of the observed sex-specific diet-BP relationships need deeper examination.
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